ClinVar Miner

Submissions for variant NM_000363.5(TNNI3):c.232A>T (p.Thr78Ser)

gnomAD frequency: 0.00001  dbSNP: rs786204399
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003183409 SCV003869200 uncertain significance Cardiovascular phenotype 2022-12-07 criteria provided, single submitter clinical testing The p.T78S variant (also known as c.232A>T), located in coding exon 5 of the TNNI3 gene, results from an A to T substitution at nucleotide position 232. The threonine at codon 78 is replaced by serine, an amino acid with similar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort; however, clinical details are limited (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.
Labcorp Genetics (formerly Invitae), Labcorp RCV003586392 SCV004277445 uncertain significance Hypertrophic cardiomyopathy 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 78 of the TNNI3 protein (p.Thr78Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with TNNI3-related conditions (PMID: 30731207). ClinVar contains an entry for this variant (Variation ID: 2455516). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV004593232 SCV005078365 uncertain significance not provided 2024-07-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign in association with a TNNI3-related disorder to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30731207)
Color Diagnostics, LLC DBA Color Health RCV005403300 SCV006064022 uncertain significance Cardiomyopathy 2024-08-27 criteria provided, single submitter clinical testing This missense variant replaces threonine with serine at codon 78 of the TNNI3 protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with TNNI3-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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